Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000258550
Ethics application status
Approved
Date submitted
29/01/2024
Date registered
15/03/2024
Date last updated
15/03/2024
Date data sharing statement initially provided
15/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring how the human body responds to extreme heat as a result of climate change
Scientific title
Evaluating the human physiological heat strain responses to environmental conditions equivalent to 35 C wet-bulb temperature
Secondary ID [1] 311287 0
Nil known
Universal Trial Number (UTN)
U1111-1302-4047
Trial acronym
35CTW
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heat-related cardiovascular strain 332524 0
Heat-related thermal strain 332525 0
Heat-related changes in thermal perceptions and symptoms of distress 332526 0
Condition category
Condition code
Cardiovascular 329212 329212 0 0
Normal development and function of the cardiovascular system
Public Health 329213 329213 0 0
Other public health
Injuries and Accidents 329214 329214 0 0
Other injuries and accidents
Neurological 329215 329215 0 0
Studies of the normal brain and nervous system
Respiratory 329216 329216 0 0
Normal development and function of the respiratory system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo 7 consecutive days of exercise heat acclimation in pairs in the Thermal Ergonomics Laboratory's climate chamber (University of Sydney) set to 40 °C, 46% relative humidity (RH). The protocol will involve 90 minutes of treadmill running at an individualized target of ~70% of heart rate reserve. These sessions will be supervised by qualified research personnel (i.e., undergraduate or post PhD-level exercise science/physiology trainees), and adherence will be assessed as the number of sessions completed out of 7.

In the same pairs, participants will then undergo 3-hour (maximum) exposures to all 4 different extreme heat conditions in the climate chamber (University of Sydney), with exposures separated by at least 72 hours:
1. Hot, very humid (HVH): 38 °C, 81.1% RH (Twet equal to 35.00 °C)
2. Hot, humid (HH): 46 °C, 45.8% RH (Twet equal to 35.00 °C)
3. Very hot, dry (VHD): 54 °C, 26.2% RH (Twet equal to 34.99 °C)
4. Very hot, very dry (VHVD): 54 °C, 13.1% RH (Twet equal to 28.54 °C)
For all exposures, participants will remain seated in the chamber and will be allowed to drink water ad libitum. Intervention fidelity will be assessed through laboratory observation and monitoring by the researcher.
Intervention code [1] 327736 0
Lifestyle
Comparator / control treatment
In pairs, participants will undergo a 3-hour (maximum) exposure to hot and very humid (HVH) conditions (38 °C, 81.1% RH (Twet equal to 35.00 °C)) in the Thermal Ergonomics Laboratory's climate chamber (University of Sydney). Intervention fidelity will be assessed through laboratory observation and monitoring by the researcher.
Control group
Active

Outcomes
Primary outcome [1] 337051 0
Core temperature (Trec)
Timepoint [1] 337051 0
Every 5 seconds throughout the exposure for each condition
Primary outcome [2] 337052 0
Heart rate
Timepoint [2] 337052 0
Every 1 second throughout the exposure for each condition
Primary outcome [3] 337053 0
Whole-body sweat loss
Timepoint [3] 337053 0
Body mass measurement pre- and post-exposure, and fluid and urine measurements as needed (when participant drinks water or needs to urinate) throughout the exposure for each condition
Secondary outcome [1] 430486 0
Mean skin temperature
Timepoint [1] 430486 0
Every 5 seconds throughout the exposure for each condition
Secondary outcome [2] 430487 0
Blood pressure
Timepoint [2] 430487 0
Every 10 minutes throughout the exposure for each condition
Secondary outcome [3] 430491 0
Blood gases (pH, PO2, and PCO2)
Timepoint [3] 430491 0
Every 60 minutes throughout the exposure for each condition
Secondary outcome [4] 430493 0
Signs and symptoms of distress
Timepoint [4] 430493 0
Every 20 minutes during exposures and exercise heat acclimation, with increasing frequency up to every 3 minutes if/when signs or symptoms begin to manifest
Secondary outcome [5] 432819 0
Mean skin temperature
Timepoint [5] 432819 0
Every 60 minutes throughout the exposure for each condition

Eligibility
Key inclusion criteria
18-40 years old
Generally healthy
Able to read and understand English in order to provide informed consent to participate in the study
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Those with contraindications to rectal temperature measurement (e.g., haemorrhoids, heterotopic ossification, rectal bleeding or bleeding disorder, fissures or active infections, anticoagulant therapy, colitis)
Smokers
Pregnancy
Currently diagnosed or those that possess a history of hypertension, cardiovascular, respiratory and/or metabolic disorders
Medication use related to any of the above conditions

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation) for N=12 which will then be mirrored between sexes
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Sample Size Justification
Sample size was determined a priori based on expected differences across conditions and the minimally clinically important difference between sexes in the rates of core temperature change in response to the exposures. Using a simulation-based R package, we entered the following information: (1) anticipated rates of change (°C/h) of 0.49 and 0.57 for HVH, 0.67 and 0.75 for HH, and 0.86 and 0.93 for VHD and VHVD in males and females, respectively; (2) a common standard deviation of 0.05 °C/h based on typical measurement error; (3) a level set at 0.05; and (4) N = 12 per group. These parameters yielded >80% power to detect differences between all relevant comparisons.

Statistical Analysis
For each trial, the exposure times to reach a Trec of 39.0 °C will be compared across conditions with a one-way ANOVA. If the Trec target is not attained, the rate of change in Trec in the final hour of the trial will be used to calculate the predicted time to reach 39.0 °C.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2024
Actual
Date of last participant enrolment
Anticipated
2/12/2024
Actual
Date of last data collection
Anticipated
20/12/2024
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315540 0
Government body
Name [1] 315540 0
National Health and Medical Research Council
Country [1] 315540 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney, Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 317630 0
None
Name [1] 317630 0
Address [1] 317630 0
Country [1] 317630 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314440 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 314440 0
Research Integrity and Ethics Administration; Level 3, F23 Administration Building, The University of Sydney, Camperdown, NSW 2006
Ethics committee country [1] 314440 0
Australia
Date submitted for ethics approval [1] 314440 0
23/10/2023
Approval date [1] 314440 0
20/12/2023
Ethics approval number [1] 314440 0
2023/884

Summary
Brief summary
Climatologists currently estimate that the environmental threshold for human heat tolerance is 6 hours at a wet-bulb temperature (Twet) of 35 °C. When accounting for human physiological thermoregulatory variables such as metabolic heat production and sweating capacity, however, it is likely that this threshold is severely underestimated. Contrary to the assumptions made by the 35 °C Twet model, in real-world scenarios, people expend anywhere between 1.5 to 5.0 METs to perform activities of daily living, and the ability to cool down through sweating is limited in certain conditions. Specifically, in very humid environments, evaporative capacity is limited by a low vapour pressure gradient between the air and skin; whereas in very dry environments, it is limited by the ability of the body to produce sweat. This is an important distinction because the same Twet can be represented by different combinations of air temperature and relative humidity, which means that the limiting factor to achieving heat balance will be different depending on the environmental conditions being experienced. It is more than likely that the limits to human heat tolerance are not represented by a universal Twet temperature threshold, but rather differ based on the type of heat stress an individual is exposed to (i.e., humid vs. dry). This theory has only ever been modelled and has never been tested in human subjects which is imperative to moving this area of research forward.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131590 0
Prof Ollie Jay
Address 131590 0
Thermal Ergonomics Laboratory (Room 901), Susan Wakil Health Building, The University of Sydney, Camperdown, NSW 2006
Country 131590 0
Australia
Phone 131590 0
+61 293519328
Fax 131590 0
Email 131590 0
[email protected]
Contact person for public queries
Name 131591 0
Prof Ollie Jay
Address 131591 0
Thermal Ergonomics Laboratory (Room 901), Susan Wakil Health Building, The University of Sydney, Camperdown, NSW 2006
Country 131591 0
Australia
Phone 131591 0
+61 293519328
Fax 131591 0
Email 131591 0
[email protected]
Contact person for scientific queries
Name 131592 0
Prof Ollie Jay
Address 131592 0
Thermal Ergonomics Laboratory (Room 901), Susan Wakil Health Building, The University of Sydney, Camperdown, NSW 2006
Country 131592 0
Australia
Phone 131592 0
+61 293519328
Fax 131592 0
Email 131592 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data will be available in published study results.
When will data be available (start and end dates)?
Data will be available immediately following publication (no end date).
Available to whom?
Data will be available within published journals and case by case at the discretion of the primary sponsor.
Available for what types of analyses?
Meta-analysis
How or where can data be obtained?
Access to data is subject to approval by the Principal Investigator with a requirement to sign a data access agreement. Access can be obtained by emailing Prof Ollie Jay at [email protected].


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.